BPH: Alpha-Blockers May Increase Stroke Risk in Some Men

Ricki Lewis, PhD

December 09, 2015

Older first-time users of alpha-blockers for benign prostatic hyperplasia (BPH) have increased risk for ischemic stroke if they are not already taking antihypertensives, according to a study published online December 7 in the Canadian Medical Association Journal.

Chao-Lun Lai, MD, PhD, from the Department of Internal Medicine and Center for Critical Care Medicine, National Taiwan University Hospital, and coworkers used a self-controlled case series design to assess the risk for first-time use of alpha-blockers in men aged 50 years or older. The drugs are strong vasodilators and are known to cause dizziness and hypotension at first use ("first-dose effect"). Manifestations include syncope, fractures, and ischemic stroke from acute cerebral hypoperfusion.

"The association between alpha-blocker therapy and ischemic stroke was driven mostly by the prescription of alpha-blockers following a previous ischemic stroke," the investigators note. The risk was especially apparent among those not taking antihypertensives, and the authors recommend caution in prescribing alpha-blockers in this group.

Although alpha-blockers were developed as antihypertensive drugs, they began to be used to treat BPH in 1976. Their primary use now is for BPH because other drugs have proved more effective in lowering blood pressure.

Using Taiwan's National Health Insurance claims database, the investigators evaluated 7502 Taiwanese men older than 50 years (mean age, 71 years) who began use of alpha-blockers from 2007 to 2009 for BPH and suffered ischemic stroke. The study design followed risk periods before or after first alpha-blocker dispensing date (index date). Preexposure period 1 was within 21 days before the index date; preexposure period 2 was 22 to 60 days before the index date. Postexposure period 1 was within 21 days after the index date, and postexposure period 2 was 22 to 60 days after. The "unexposed" period was defined as 60 days before and after the preexposure and postexposure periods, respectively. The investigators used a conditional Poisson regression model to estimate incidence rate ratio (IRR) of ischemic stroke in each risk period relative to the unexposed period.

The study compared results for all participants and for those taking other antihypertensives. For all patients, risk for ischemic stroke increased for 21 days after the start of alpha-blocker therapy compared with risk during the unexposed period (adjusted IRR, 1.40; 95% confidence interval [CI], 1.22 - 1.61). The risk was also significantly higher in preexposure risk period 1 (adjusted IRR, 2.87; 95% CI, 2.60 - 3.17) and preexposure risk period 2 (adjusted IRR, 1.99; 95% CI, 1.82 - 2.18). Incidence of ischemic stroke in postexposure risk period 2 was lower than in the unexposed period (adjusted IRR, 0.80; 95% CI, 0.70 - 0.92).

For men taking other antihypertensives, incidence of ischemic stroke in postexposure risk period 1 was similar to that in the unexposed period (adjusted IRR, 1.07; 95% CI, 0.88 - 1.29). However, incidence in postexposure risk period 2 was significantly lower than in the unexposed period (adjusted IRR, 0.67; 95% CI, 0.56 - 0.81).

Among patients not taking other antihypertensives, incidence of ischemic stroke was significantly higher in postexposure risk period 1 than in the unexposed period (adjusted IRR, 2.11; 95% CI, 1.73 - 2.57), whereas the incidence in postexposure risk period 2 was similar to that in the unexposed period (adjusted IRR, 1.06; 95% CI, 0.86 - 1.31). The risk for stroke was elevated in this patient group in both preexposure 1 and preexposure 2 periods (adjusted IRR, 1.89 [95% CI, 1.61 - 2.22] and 2.71 [95% CI, 2.27 - 3.24], respectively.)

The authors suggest their findings support the first-dose effect hypothesis.

As for the elevated preexposure risk, they write, "Significantly high IRRs in the 2 pre-exposure risk periods reflected the prescription pattern of α-blocker therapy frequently being started after an ischemic stroke." They note that elevated blood pressure or urinary symptoms following an ischemic stroke may explain the prescription pattern.

The researchers conclude that "only patients without concomitant exposure to other antihypertensive agents had an increased risk of ischemic stroke during the early initiation period of α-blocker therapy." They hypothesize that those at highest risk are normotensive.

Limitations of the study include the inability to determine whether patients had actually taken medications and generalizability to other populations.

The researchers have disclosed no relevant financial relationships.

CMAJ. Published online December 7, 2015. Full text

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